GST-HG141 for people with chronic hepatitis B who have not had an adequate response to antiviral treatment

A Randomized, Double-Blind, Placebo-Controlled, Multi-Center Phase III Trial of GST-HG141（Neracorvir）for Combination Therapy (add-on) in Patients With Inadequate Response to Antiviral Drugs in Chronic Hepatitis B (CHB)

This trial will test whether adding GST-HG141 helps people with chronic hepatitis B who still have detectable virus despite at least a year on standard antiviral medication.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 526 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Fujian Akeylink Biotechnology Co., Ltd. (Industry-sponsored)
• Locations: 1 site (Hangzhou, Zhejiang)
• Trial ID: NCT07090759 on ClinicalTrials.gov

What this trial studies

This randomized, double-blind, placebo-controlled phase III trial enrolled 526 HBeAg-positive chronic hepatitis B patients with an inadequate response to nucleos(t)ide analogue therapy and randomized them 1:1 to GST-HG141 or matching placebo while they continued their background antiviral drug. The study measures antiviral efficacy (including HBV DNA levels and HBeAg status), safety, and population pharmacokinetics. Eligible participants were adults 18–70 years with HBV DNA >50 IU/mL, on the same NA monotherapy for at least 3 months and on NA therapy for over one year, with ALT ≤5×ULN. Treatments and outcomes were compared between the GST-HG141 and placebo groups under double-blind conditions to determine benefit and tolerability.

Who should consider this trial

Good fit: Adults 18–70 years who are HBeAg-positive with HBV DNA >50 IU/mL despite >1 year of continuous nucleoside analogue therapy (same NA for ≥3 months before screening), meeting the study's weight/BMI and ALT criteria, are ideal candidates.

Not a fit: People who already have sustained viral suppression on antiviral therapy, are HBeAg-negative, or who have decompensated liver disease or other exclusions may be unlikely to benefit from this add-on treatment.

Why it matters

Potential benefit: If successful, GST-HG141 could help reduce viral levels and improve treatment response for patients who are not fully controlled on current antiviral therapy.

How similar studies have performed: Adding new agents to nucleos(t)ide analogue therapy has produced mixed results historically, and GST-HG141 represents a novel candidate being tested in a phase III program.

Eligibility criteria

Inclusion Criteria:

1. Male or female individuals aged 18-70 years (inclusive of the boundaries);
2. Male weight ≥ 50 kg, female weight ≥ 45 kg, with a body mass index (BMI) within the range of 18-35 kg/m2 (inclusive of the boundaries);
3. Have been continuously taking nucleoside analogues (entecavir \[ETV\], tenofovir disoproxil fumarate \[TDF\], emivirofavir \[TMF\], or propivirofavir \[TAF\]) for more than one year (with a break of less than one month in the past year), and are receiving treatment at the time of screening and agree to accept the treatment plan provided by this study during the study period;

   \* Have maintained the same NA monotherapy for more than 3 months before screening
4. HBeAg positive, serum HBV DNA can be detected by high-sensitivity PCR, and HBV DNA \> 50 IU/mL;
5. At the time of screening, ALT ≤ 5×ULN;
6. Male participants with a fertile female partner or female participants of childbearing age who are willing to voluntarily take effective contraceptive measures from the time of screening until 28 days after the completion of the study ;
7. Sign the informed consent form before the trial and be able to complete the study as required by the trial protocol.

Exclusion Criteria:

1. History of life-threatening severe allergic reactions such as anaphylactic shock, or allergy to the active ingredients or excipients of the study drug as suspected by the investigator;
2. Concomitant use of cytochrome P450 enzyme 3A4 (CYP3A4) inhibitors, inducers, or substrates within 28 days prior to screening;
3. Systemic use of immunosuppressants, immunomodulators (interferon must be discontinued for more than 12 months), or cytotoxic drugs within 6 months prior to screening; or vaccination with live attenuated vaccines within 1 month prior to screening;
4. Presence of acute infections requiring treatment prior to randomization;
5. Clinically significant acute or chronic liver disease not caused by HBV infection, rendering the subject unsuitable for participating in the study as determined by the investigator;
6. Subjects with a history of cirrhosis (e.g., subjects who have undergone pathological examination of liver tissue with a report indicating cirrhosis or those who have undergone endoscopy indicating esophageal or gastric varices); or subjects with currently diagnosed or suspected decompensated cirrhosis, including but not limited to: hepatic encephalopathy, hepatorenal syndrome, bleeding from esophageal or gastric varices, splenomegaly, and ascites; or subjects with significant progression of liver fibrosis;
7. Primary liver cancer; serum alpha-fetoprotein (AFP) greater than 20 μg/L (or 20 ng/mL) or DCP\>40 mAU/mL or imaging suggesting possible malignant lesions in the liver; concurrent other malignancies or history of other malignancies within the past 5 years (except for cured basal cell carcinoma or squamous cell carcinoma of the skin and cervical carcinoma in situ);
8. Presence of gastrointestinal impairment or gastrointestinal disease that may affect the absorption of oral medication in the judgment of the investigator, such as severe gastrointestinal diseases (peptic ulcer, erosive or atrophic gastritis), partial gastrectomy, Grade \> 2 gastrointestinal symptoms at screening (e.g., nausea, vomiting, or diarrhea), etc.;
9. Concurrent severe diseases of the circulatory, respiratory, urinary, hematologic, metabolic, immune, psychiatric, neurological, renal, or other systems, rendering the subject unsuitable for participating in the study as determined by the investigator.
10. Subjects with major trauma or major surgery within 3 months prior to screening; or those who plan to undergo surgery during the study period;
11. Laboratory tests:

    1. Platelet count \< 100 × 109/L;
    2. White blood cell count \< 3.0 × 109/L;
    3. Absolute neutrophil count \< 1.3 × 109/L;
    4. Serum total bilirubin \> 2× ULN;
    5. Albumin \< 35 g/L;
    6. GFR ≤ 60 mL·min-1·(1.73 m2)-1 (calculated using the CKD-EPI formula);
    7. International normalized ratio (INR) of prothrombin time \>1.5;
12. Positive for hepatitis C antibody, positive for HIV antigen/antibody, or positive for syphilis antibody with a positive RPR or TRUST test result;
13. History of sustained alcohol abuse within the past 3 years (weekly alcohol intake \> 14 units, where 1 unit of alcohol equals 1 bottle of 350 mL beer, 120 mL wine, or 30 mL of spirits at 40% alcohol content);
14. History of drug dependence or substance abuse;
15. Participation in clinical trials involving other investigational drugs or medical devices and receiving the investigational drug or using the medical device within 3 months prior to screening;
16. Women who are breastfeeding or tested positive for pregnancy;
17. Determined by the investigator to be unsuitable for this trial for any other reasons.

Where this trial is running

Hangzhou, Zhejiang

• Shulan(Hangzhou) Hospital — Hangzhou, Zhejiang, China (Recruiting)

Study contacts

• Study coordinator: Yan wenhao, MD

Conditions Chronic Hepatitis b